FEDERAL COURT OF AUSTRALIA

Aktiebolaget Hässle v Alphapharm Pty Ltd

[1999] FCA 1394

INTELLECTUAL PROPERTY – patents – pharmaceutical formulation – infringement – combination patent – whether, assuming patent to be valid, respondent has taken each essential integer, or mechanical equivalent thereof, of patentee’s claim

WORDS AND PHRASES – “mechanical equivalents”

Nicaro Holdings Pty Ltd v Martin Engineering Co (1990) 91 ALR 513 applied

AKTIEBOLAGET HÄSSLE AND ASTRA PHARMACEUTICALS PTY LIMITED v ALPHAPHARM PTY LIMITED

NG 884 OF 1998

LEHANE J

SYDNEY

12 OCTOBER 1999

REASONS FOR JUDGMENT

[Note:  This is an edited version of reasons for judgment delivered, initially, on a confidential basis.  It incorporates certain changes, the purpose of which is to avoid public disclosure of information claimed to be confidential.  The changes do not affect the substance of the reasons]

1                     The nature of this proceeding and the issues in it are described in reasons for judgment, published 12 May 1999, dealing with a cross‑claim for revocation of the patent in suit.  Those reasons should be read with these; I shall refer in these reasons, in the same way as in the published reasons, to the parties, the patent, the Alphapharm product and other matters.

Legal principles

2                     There is no issue about the applicable law.  The first step is to construe the claims.  In the course of my reasons for judgment on the cross‑claim, I have discussed a number of the questions of construction which arise.  The patent is a combination patent.  What a patentee must prove in order to establish infringement was described by Gummow J (in the context of anticipation) in Nicaro Holdings Pty Ltd v Martin Engineering Co (1990) 91 ALR 513 at 527, 528:

“… to establish infringement of a combination patent the patentee must show that the defendant has taken each and every one of the essential integers of the plaintiff's claim; if on its true construction the claim is for a particular combination of integers and the alleged infringer omits one of them, the infringer escapes liability: Populin v H B Nominees Pty Ltd (1982) 59 FLR 37 at 41 . Further, where what is in question is an inessential integer, a device which contains the essential integers will fall within the claim, whether or not an inessential integer is replaced by an obviously equivalent device or omitted altogether; hence, the expression ‘mechanical equivalent’ …”

The Alphapharm product

3                     Alphapharm admits on the pleadings that, upon the later occurring of the grant of approval of the Alphapharm product by the Therapeutic Goods Administration and the expiry of the term of the compound patent, Alphapharm will import the Alphapharm product into Australia or make or authorise others to make it, will sell or otherwise supply it in Australia, will keep it in Australia for the purpose of sale or supply, authorise other persons to sell or supply it in Australia or keep it for sale or supply in Australia, will authorise other persons to use the Alphapharm product in Australia for treatment of gastrointestinal diseases and will otherwise exploit the Alphapharm product in Australia.  Accordingly, if the Alphapharm product falls within one or more of the product claims of the patent, there will be infringement; equally if the process by which it is prepared falls within one of the process claims.  Assuming the validity of claim 17, there would also necessarily be an infringement of that claim if (but only if) the Alphapharm product infringed at least one of the product claims.

4                     Alphapharm has also admitted a number of facts concerning the Alphapharm product.  It is convenient to set out in full the admissions contained in Alphapharm’s notice admitting facts dated 23 November 1998.

“The Respondent admits for the purpose of these proceedings only that:

1       (a)       the Alphapharm Product is an oral pharmaceutical preparation;

         (b)       the Alphapharm Product is in the form of pellets contained within a capsule, which pellets are of a different shape to pellets produced according to the Patent;

         (c)        the pellets contain omeprazole as the active ingredient;

2       (a)       the pellet has a core comprising a sugar sphere;

         (b)       the sugar core is coated with three layers.

            [In what follows, ‘first coating layer’ means the coating layer immediately outside the sugar sphere; ‘second coating layer’ means the coating layer immediately outside the first coating layer, and ‘third coating layer’ means the coating layer immediately outside the second coating layer.]

3          (a)       the first coating layer contains omeprazole;

            (b)       the first coating layer contains talc as an anti‑adherent;

4         (a)        the second coating layer contains hydroxypropyl methylcellulose (HPMC) (also known as hypromellose);  

            (b)       HPMC is polymeric;

            (c)        HPMC is water soluble;

            (d)       HPMC is a filmforming compound;

            (e)        HPMC is used as a tablet excipient;

            (f)        HPMC is rapidly disintegrating in water;

5          (a)       the third coating layer contains methacrylic acid copolymer;

            (b)       methacrylic acid copolymer is used in enteric coatings;

            (c)        the third coating layer is an enteric coating;

            (d)       the third coating layer contains triethyl citrate; and

            (e)        triethyl citrate is a plasticiser.”

5                     Alphapharm has provided what it says are details of its formulation in a document headed “Formulation and manufacturing details”.  Beneath the heading “FORMULATION DETAILS” appears the following:

“Ingredient                                                     Function

Omeprazole (micronised)                                 Active

Hypromellose                                                   Coating material

Talc‑Purified                                                    Anti‑adherent

Titanium dioxide                                              Colour

Methacrylic acid copolymer                            Filming agent

Triethyl citrate                                                 Plasticiser

Sugar Spheres                                                  Support”

6                     The material before the Court demonstrates that the Alphapharm product does not have a core of the same kind as that which is described in the patent.  A sugar pellet is coated with mixture said to comprise, in addition to omeprazole, HPMC, talc and purified water.  A second coating is then applied containing HPMC (which is a polymeric filmforming compound and is water soluble); the second layer is said also to contain talc and titanium dioxide.  Finally a third coating layer is applied which is an enteric coating.

7                     Three questions are controversial.  First, what is the “core” of the Alphapharm product?  Secondly, if the core includes the first coating layer (containing omeprazole), does the core contain also an alkaline reacting compound?  Thirdly, is the “second coating layer” “inert reacting”?  If the core is to be taken to include the “first coating layer”, and the second and third questions are answered “yes”, then what Alphapharm threatens to do would infringe claim 1 and claims 4, 9 and 12.  There would also, no doubt, be infringements of the process and method of treatment claims.  There are some further issues which would arise only if claim 1 were invalid but claim 5, claim 6, claim 10 or claim 11 were not.  Those questions are: does the “core material” of the Alphapharm product include “a pH‑buffering alkaline compound rendering to the microenvironment of omeprazole a pH of 7‑12”?  Does the water content of the final dosage form of the Alphapharm product not exceed 1.5 per cent by weight?  Is the second sub‑coating layer of the Alphapharm product not less than two microns thick?

8                     Tests of samples of the Alphapharm product were conducted by Dr Lindquist at Astra’s premises in Sweden; those tests were conducted in accordance with particulars of proposed experiments served by Astra on Alphapharm and with directions of the Court; similarly, tests were conducted in Brisbane on, principally, what were claimed to be components of the Alphapharm product; those tests were conducted in accordance with particulars of proposed experiments served by Alphapharm on Astra and with directions of the Court.  Finally, Dr Lindquist conducted some further tests on samples of the Alphapharm product at Astra’s premises.  It will be necessary to consider some aspects of those tests in connection with the second of the principal matters in controversy and also in connection with some of the subsidiary questions.

Core or “core material”

9                     The evidence made it quite clear, and there is no controversy about it, that a pellet may be made which incorporates or is coated with a mixture including a drug, to which an enteric coat and any intermediate coats may then be applied, in either of two ways.  One is extrusion and spheronization, in which the core is formed from a wet mass of the active substance and other components.  The use of that method is contemplated by the specification.  The material under the heading “Cores” contemplates a mixture of the components and then says:

“The powder mixture is then formulated into small beads i.e. pellets, or tablets by conventional pharmaceutical procedures.  The pellets or tablets are used as cores for further processing.”

More specifically, the manufacture of the exemplified pellets is described as follows:

“The dry ingredients (I) were premixed in a mixer.  Addition of a granulation liquid (II) containing suspended omeprazole was made and the mass was wet‑mixed to a proper consistency.  The wet mass was pressed through an extruder and spheronized to pellets.  The pellets were dried and classified into suitable particle size ranges.”

            The other process is the one used in making the Alphapharm product.  That process involves the application of a coat containing the active substance to what is called a “non pareil”.  In the case of the Alphapharm product, the sugar pellet or seed is the non pareil.  It is common ground that “core material” is not a term of art.  Nevertheless, the experts expressed views as to its meaning, those called by Astra saying that they understood the “core” of the Alphapharm product to be the sugar non pareil coated with the mixture containing omeprazole and (except Dr Marshall) those called by Alphapharm expressing the view that the “core” of the Alphapharm product was the non pareil only.  The divergence is summarised in the following passage in Dr Ashley’s evidence:

“I agree with Professor Rees when he says … that ‘a common usage of the word ‘core’ in the field of pharmaceutical formulation’ is to specify ‘an object to which a coating is applied’.  In the Alphapharm product, there could be three such ‘cores’:

(a)       the sugar sphere;

(b)       the sugar sphere coated with the ‘inner layer’; and

(c)        the sugar sphere coated with the ‘inner layer’ and the ‘middle layer’.

In my view, Professor Rees’ choice of (b) as the ‘relevant core material’ of the Alphapharm product depicts the latter as identical in structure to the product described in claim 1 of the Formulation Patent.  That is clearly not so.  In the Formulation Patent, the core is depicted as an homogenous central sphere containing the medicament.  In the Alphapharm product, there is no such region, because the core contains no medicament, and is simply a support for successively applied coating layers.”

10                  Once again, Dr Marshall was the only expert substantially sheltered from knowledge of the matters in controversy and his evidence relevant to the present question, though not of course specifically directed to it, is interesting.  Again both parties sought to take advantage of it.  In his third report Dr Marshall discussed the two basic steps comprising a formulation process of an enteric coated dosage form.  The first step was the manufacture of a “core” granule.  That could be done by extrusion and marumerization (as I understand it, a form of spheronization).  Dr Marshall continued:

“A modification on this process is the use of sugar seeds of defined diameter as cores and the rolling or building of active material upon the seed in a ‘snowball’ effect using a granulating solution.”

11                  That seems to favour the view propounded by Alphapharm.  Dr Marshall, however, proceeds to use the expression “core granules” to describe indifferently a spheronized pellet and a coated sugar seed.  It is clear at least from Dr Marshall’s evidence that he regards the two processes as alternative ways of doing what is substantially the same thing.  There is nothing in the other evidence, in my view, which throws any doubt on that way of looking at the matter.  There may be room for argument about which process is better suited to the formulation of a particular drug.  Dr Pilbrant thought that, for omeprazole, extrusion and spheronization was probably the better method because it (in his view) allowed for more immediate exposure of a greater number of omeprazole particles to the fluids in the intestine.  Dr Story, on the other hand, thought that the application of a coat to a non pareil was a better and more “elegant” approach and, because it reduced the number of excipients required (because there was no need to produce a “wet mass” for extrusion), reduced the number of possible mechanisms by which the omeprazole might degrade.  But that evidence, I think, merely reinforces the general point: a pellet, carrying the active drug, may be produced by either of the two methods (there may be others); a particular formulator may prefer one or the other for a particular drug.  But often, if not usually, either may be used.

12                  Those considerations do not conclusively answer the question, what is the “core” of the Alphapharm product, or which are its “core materials”?  Counsel for Alphapharm referred me to the definition in the Macquarie Dictionary, 3^rd Ed, which includes “the central, innermost, or most essential part of anything” and gives, as an example, the core of a curriculum.  The ninth of the meanings given by the Shorter Oxford English Dictionary, 3^rd Ed, is “the innermost part or heart of anything”.  The sugar seed is undoubtedly the innermost part of the Alphapharm product, but would not ordinarily be described as its most essential part or its literal or figurative heart.  Those descriptions, in my view, much more naturally describe the sugar seed coated with the mixture incorporating omeprazole.  Equally, the components of that mixture are, in my view, properly described as “core materials”.

13                  The circumstance that the body of the specification describes, particularly in example 2, the process of extrusion and spheronization as that applied in making the exemplified pellets does not, in my view, require the claims to be read down so that “core” and “core material” are to be taken as referring only to a pellet, and its components, made by that method.  The authorities which I have already cited make it clear that one does not read down the clear language of a claim by reference to a description in the body of the specification; and, for the reasons I have given, I do not think there is any serious doubt that “core material” refers to the components, including the active drug, of a pellet to which a sub‑coat and an enteric coat are then applied.  Even if that were not so, however, this, in the light of the evidence to which I have referred, is clearly a case of “mechanical equivalents”.

Alkaline reacting compound

14                  The formulation and manufacturing details provided by Alphapharm, in relation to its product, describe the first (active) coat as comprising omeprazole, HPMC and purified talc.  Experiments were conducted in Sweden to measure the pH of the first coating layer (containing omeprazole) of the Alphapharm product and also to measure the pH of pure omeprazole.  The Brisbane tests included measurement of the pH of a mixture, made for the purpose of the test, of what were said to be samples of the actual components of the first coating layer of the Alphapharm product.  A further test was made after sugar spheres had been added to that mixture, which was then stirred for ten minutes.  It is unnecessary, at this stage, to discuss the substantially controversial aspects of any of the experiments, but some of the reported results are important.  In Sweden, Dr Lindquist measured a sample (it was suggested in evidence led by Alphapharm that the sample may have been contaminated by particles of other layers) of the inner, omeprazole‑containing, layer of the Alphapharm product, to which four microlitres of de‑ionised water had been added.  To perform the test, Dr Lindquist used an ISFET (ion selective field effect transistor) pH electrode connected to a pH meter.  The pH thus measured was 8.8.  Dr Lindquist also tested the pH of pure omeprazole mixed with de‑ionised water.  The reported result was a pH of 6.4.  He also performed a theoretical calculation based on the particular properties of omeprazole reported in Pilbrant and Cederberg, which produced the same result.  In the later tests in Sweden, Dr Lindquist substantially replicated those results, testing the pH of the inner coat of the Alphapharm product and of pure omeprazole by the use of a “phenol red” indicator.  The Brisbane tests did not include a measurement of the pH of pure omeprazole.  Whatever conclusion one might reach about other aspects of the experiments in Sweden, the criticisms made of the measurement of the pH of pure omeprazole do not convince me that I should not accept that the pH of a saturated solution of omeprazole is approximately 6.4.  Indeed, there seemed to be no serious dispute about that.  The Brisbane experiments measured the pH of the mixture of purified water, omeprazole, HPMC and talc at a value greater than 7 but less than 8. The pH of the mixture to which sugar spheres were added was less, but nevertheless still above 7.

15                  In that state of affairs, Astra’s submission is simple: the pH of omeprazole is 6.4.  If Alphapharm’s evidence is accepted, the pH of the inner coating layer of the Alphapharm product is greater than 7 (if the results of Dr Lindquist’s test are accepted, it is 8.8).  The fact that the pH of the inner coat exceeds 7 demonstrates that it incorporates an alkaline reacting compound.  It does not matter if in fact the only compound present in the mixture which might raise the pH above 7 is talc; if talc has that effect in the mixture, then it is an alkaline reacting compound.

16                  I have already expressed views, in dealing with the suggestion that the patent is bad for ambiguity, about the meaning of the phrase “alkaline reacting compound” as used in the claims.  It is necessary, however, to return briefly to that topic.  Talc is not listed among the substances, or categories of substances, described in the specification as examples of alkaline reacting compounds.  There is no dispute about what it is or about ways in which it is commonly used in pharmaceutical formulations.  Dr Story described its provenance and manufacture as follows:

“I note from the Handbook of Pharmaceutical Excipients that talc is produced from naturally occurring hydropolysilicate.  It is manufactured by subjecting hydropolysilicate to a flotation process to remove mineral impurities.  It is then finely powdered and treated with hydrochloric acid, washed with water and dried.”

17                  Different grades of talc are available.  A monograph on talc included in the Handbook of Pharmaceutical Excipients, 1994, lists, under the heading “Typical Properties”, a pH range of 6.5 to 10.  Among other things, talc is used as a lubricant or glidant in tablet or capsule manufacture, as filler for tablets and capsules and, of course, as a dusting powder.  The specification lists talc as an “additive” which might be included in the sub‑coat and suggests that it may be included, as a dispersant, in the enteric coat.  Talc is included in each of the seven formulations of a tablet core in table 1 of example 1 in the specification.  The Handbook tells us that talc is practically insoluble in dilute acids and alkalis, organic solvents and water.

18                  No test conducted by either party identified any component of the Alphapharm product’s core materials other than those listed in Alphapharm’s formulation details.  (Dr Lindquist knew that talc was included, and suspected the presence of HPMC).  The only relevant tests were the measurement of the pH of a solution of pure omeprazole, on the one hand, and the measurements of the pH of the inner coat of the Alphapharm product and of the mixture of the components of that coat on the other.  Thus, relevantly, all that is known is that there is a component in the coat which raises the pH of an omeprazole solution to a value greater than 7 (or, if the accuracy of Dr Lindquist’s test is accepted, 8.8).  Significantly, no property of a component of the Alphapharm product’s core material is revealed by those tests other than the property that it raises the pH of an aqueous solution of omeprazole.  Nothing is shown as to how (if at all) such a component may react with other substances or in other contexts.  One other fact is known, which may be relevant.  The Brisbane experiments included one which involved testing the acid absorbance of the grade of talc said to be used in the Alphapharm product and a number of alkaline reacting compounds of kinds referred to in the specification.  In brief summary, the result was that the acid absorbance of the talc was revealed to be extremely slight (though apparently not entirely non‑existent) and very much less than that of any of the other compounds tested (among which there was a substantial range of capacity to absorb acid).

19                  The substantial issue on this part of the case, then, is whether a compound, the only known property of which is that it will raise above 7 the pH of an omeprazole solution, is an alkaline reacting compound within the claims of the patent, particularly claim 1.  In considering that question it is unnecessary to form any view about the relative reliability of the tests in Sweden and the Brisbane tests.  (In cross‑examination, Dr Lindquist gave evidence which, senior counsel for Alphapharm submitted, was to the effect that a compound whose pH in suspension or solution was measured at 7.98 might, when added to a solution of omeprazole – pH 6.4 – produce a mixture the pH of which exceeded 7.98 and might be as high as 8.8.  A reading of that evidence as a whole suggests, however, that that would be so only if the measured suspension or solution was considerably less concentrated than the mixture).  Certainly, if the result of the Swedish tests was accurate, the pH of the inner layer of the Alphapharm product is undeniably alkaline, even on an expanded view of a “neutral range”, whereas the pH value resulting from the Brisbane test might, on some of the evidence, be regarded as falling within such a range.  For reasons which will appear, however, that in my view does not matter.

20                  The evidence of the experiments and of the formulation of the Alphapharm product raises, in an acute form, the question whether the view which I have expressed as to the meaning, in the claims, of the phrase “alkaline reacting compound” is literally correct.  It is by no means an easy question.  I have no doubt, having read and heard the evidence, that if one were to ask a formulator, or a pharmaceutical chemist, to provide a list of alkaline reacting compounds, it is highly unlikely that it would occur to the formulator to include talc of any grade.  Equally, if the formulator were seeking a compound which would protect omeprazole against encroaching acid, talc would be among the last substances that the formulator would think of (indeed talc probably would not cross the formulator’s mind).  Talc, as I have mentioned, is not among the alkaline reacting compounds specifically mentioned in the specification, though it is included in the tablet core formulations in example 1 and is suggested as an excipient to be included in the sub‑coat and the enteric coat.  Talc is barely soluble in water; and it is widely used for purposes ordinarily best served (the evidence suggests) by substances which are at least substantially inert.

21                  On any view, however, there is equally no serious doubt that the particular talc raises the pH of an omeprazole solution above 7, slightly so even when sugar seeds are included in the mixture.  I think I must conclude on the evidence that a compound which will increase the pH of the omeprazole above 7 must itself have a pH over 7.  Dr Lindquist made that clear in re‑examination and his evidence in cross‑examination does not suggest the contrary.  The only other evidence on that subject is that of Professor Rees who was asked – no doubt deliberately – a rather different question:

“Q.      But it is possible to have a compound of a pH less than 7 that would raise the pH of omeprazole above 6.4?

 A.       Yes.”

22                  I conclude, therefore, that the core of the Alphapharm product includes a compound which satisfies the definition supported by Professors Rees and Brown.  The evidence does not establish that it contains a compound which meets the definition supported, at least, by Dr Story, Dr Rowe and Dr Ashley.

23                  I have already held that the “alkaline reacting compound” of the claims is the substance described in the specification as “an alkaline reacting, otherwise inert, pharmaceutically acceptable substance (or substances), which creates a ‘micro‑pH’ around each omeprazole particle of not less than pH = 7, preferably not less than pH = 8, when water is absorbed to the particles of the mixture or when water is added in small amounts to the mixture”.  In other words, I accept that an alkaline reacting compound is an alkali which, in the final mixture, produces that result.  There is a substance in the core of the Alphapharm product – probably talc – which produces that result.

24                  Clearly, the purpose of the alkaline reacting compound is to stabilise the omeprazole.  It was submitted that talc would not perform that function because it will absorb very little acid, if any; and because, as the patent tells us:

“Omeprazole is susceptible to degradation/transformation in acid reacting and neutral media.  The half‑life of omeprazole in water solutions at pH‑values less than four is shorter than ten minutes.  Also at neutral pH‑values the [degradation] reaction proceeds rapidly.  The stability profile is similar in the solid phase.  The degradation of omeprazole is catalyzed by acidic reacting compounds and is stabilized in mixtures with alkaline reacting compounds.  The stability of omeprazole is also affected by moisture and organic solvents.” 

25                  Thus, it was said, talc plainly cannot have been contemplated as an alkaline reacting compound, because it will not do what is required.  But the degradation results reported in Pilbrant and Cederberg and repeated in the specification refer to degradation of omeprazole in solution.  I accept Professor Rees’ evidence that the “stability profile” and “rate” of degradation are two quite different things: although the stability profile may be similar in solution and in the “solid phase”, the rate at which degradation proceeds will decrease to the extent that free water is eliminated.  That, clearly enough, is supported by the evidence that ordinarily there is no particular difficulty in applying an enteric coat directly to an alkaline or acid labile core.  If that is right, there is nothing particularly surprising in the suggestion that, provided other conditions are met, it is sufficient for the stability of a solid core that the “micro‑pH” may be as low as 7 or slightly above 7.  No doubt – as the examples in the specification suggest – relatively large quantities of a relatively strong alkaline reacting compound may be required if an enteric coat is applied directly to the core; and, if the core contains acidic substances (in addition to omeprazole), then a function required to be performed by the alkaline reacting compound may be to buffer the core against acid.  But if the core contains no acidic substance (other than omeprazole itself, which on the evidence is amphoteric) and if there is a sub‑coat separating the enteric coat from the core, then it may be (at this point exploration of the subject in evidence substantially ceased, I think) that protection is required only against very small quantities of water, the degree of protection required depending, no doubt, on the extent to which free water is eliminated from the core.

26                  In other words, the specification suggests, I think, that the essential function of the alkaline reacting compound is to produce a “micro‑pH” within the specified range.  Depending upon other aspects of the formulation the alkaline reacting compound may have other work to do and particular compounds, or particular quantities of particular compounds, may be indicated.  But the matter of immediate concern is not the variables but the essential or minimum requirement of an alkaline reacting compound: and that is that it produce the required “micro‑pH”.  On the evidence, I find that the core of the Alphapharm product includes such a compound.

Inert reacting sub‑coating layer

27                  The sub‑coating layer of the Alphapharm product is admitted to contain HPMC which in turn is admitted to be polymeric, water soluble, a filmforming compound and rapidly disintegrating in water.  It is also admitted to be a substance which is used as a tablet excipient.  The sub‑coat is claimed also to include talc (substantially in the same proportions as the “core” coat) and titanium dioxide.  It was not suggested that anything turned on the presence of titanium dioxide.  The sub‑coating layer described in claim 1 of the patent is “inert reacting” and “comprising tablet excipients which are soluble or rapidly disintegrating in water, or polymeric, water soluble, filmforming compounds, optionally containing pH‑buffering, alkaline compounds”.  It was not suggested that anything turned, in this context, on the use of the word “comprising”.  The issue is whether the Alphapharm sub‑coat is, within the meaning of claim 1, “inert reacting”.  Argument proceeded on the basis that a resolution of that issue depended on the character or effect of the talc.

28                  Alphapharm’s submissions, in effect, posed a dilemma.  If talc is an alkaline reacting substance, then it is such a substance used in the sub‑coat just as much as it is used in the core and therefore is not inert reacting; but if it is inert reacting in the sub‑coat; it cannot be otherwise in the core.  The problem which that argument encounters is that, unless the claim is self‑contradictory, it contemplates that an “inert reacting” sub‑coat may contain “pH‑buffering, alkaline compounds”.  It may be that the word “inert” is used in an unusual way in the claims, like some other terms.  Claim 8, it should not be overlooked, refers to “an inert, alkaline compound”.  I think Professor Brown was right when he said:

“The term ‘inert reacting subcoating layer(s)’ is used in claim 1 (and in claim 13).  It has a clear meaning in the context of the specification.  It means an inert or non‑reacting layer both with respect to the omeprazole in the core and with respect to the enteric coat.  In other words, the layer must not react with omeprazole and must not react with the enteric coat to any significant extent (i.e. so as to change the function of the enteric coat).  This is what formulators would assume.  When one reads the specification, it is clear that the term ‘inert reacting’ is used interchangeably with ‘inert’ … .”

29                  It was pointed out by senior counsel for Alphapharm that in the one example, given in the patent, of a sub‑coat containing an alkaline reacting compound, there were in fact two sub‑coats, that containing the alkaline reacting compound being separated from the enteric coat by the second sub‑coat, which contained no alkaline reacting compound.  Whether or not that is necessary may, no doubt, depend upon which particular compound is used in the sub‑coat and in what quantities.  And it may be that Professor Brown’s definition requires slight modification, so that “inert reacting” means that the coat (each of the coats, if there are several) does not react with the layer on either side of it.  But, on that view, which I accept, the Alphapharm sub‑coat is an inert reacting sub‑coat within the claims.

30                  There is a separate question whether, for the purposes of claims 5 and 6, the core of the Alphapharm product includes a “pH‑buffering alkaline compound”.  As I have said in connection with ambiguity, in my view the “pH‑buffering alkaline compound” is a sub-set of “alkaline reacting compound”.  The evidence establishes that the core of the Alphapharm product includes the latter.  Dr Lindquist’s tests do not demonstrate that it contains the former.  The Brisbane experiments indicate that the talc used has very slight acid absorbance capacity.  Dr Mary Patricia McAlernon, who gave expert evidence for Alphapharm, suggested that in fact the Brisbane experiment did not demonstrate that talc had any acid absorbance capacity at all.  Professor Rees gave evidence that it had some, though slight.  There is a question in any event, whether so slight a capacity is sufficient to permit talc properly to be classified as a “pH‑buffering alkaline compound”.  I am not satisfied that it is.  It follows that, assuming validity, I would not be prepared to find infringement of claim 5 or claim 6.

Subsidiary issues

(a)        Water content

31                  This relates to claim 10:

“A preparation according to any one of claims 1 to 9 wherein the water content of the final dosage form containing omeprazole [does] not exceed 1.5% by weight.”

32                  There are two questions: what is meant by the “final dosage form”?  And what is the percentage water content, by weight, of the final dosage form of the Alphapharm product?

33                  As to the first question, Astra submits that the final dosage form, in the case of the pellets, is the coated pellet not the capsule filled with coated pellets.  Alphapharm submits the contrary.  Neither suggested that there was any expert evidence which assisted on that point.  Certainly, I have not found anything in the evidence which assists.  The specification says, of the “Final dosage form”:

“The final dosage form is either an enteric coated tablet or in the case of enteric coated pellets, pellets dispensed in hard gelatin capsules or sachets or pellets formulated into tablets.  It is essential for the long term stability during storage that the water content of the final dosage form containing omeprazole (enteric coated tablets, or pellets) is kept low, preferably not more than 1.5% by weight.  As a consequence the final package containing hard gelatin capsules filled with enteric coated pellets preferably also contain [sic] a desiccant, which reduces the water content of the gelatin shell to a level where the water content of the enteric coated pellets filled in the capsules does not exceed 1.5% by weight.”

34                  I think that passage indicates that the contemplated “final dosage form”, in the case of pellets dispensed in capsules, is the pellets; and the last sentence makes it clear that the purpose of reducing the water content of the gelatin shell is to ensure that the water content of the pellets does not exceed 1.5 per cent by weight.  That is the way in which, in my view, the claim should be construed.  Tests of the water content of the pellets in the Alphapharm product were made in Sweden in both the first and the second series of tests.  In Brisbane, tests were made of the water content both of the pellets and of the capsule containing pellets.  The relevant tests, in my view, were those of the pellets alone.  The tests in Sweden all indicated a water content of about 1.2 per cent by weight, the mean of the second series of tests being 1.217 per cent.  The Brisbane tests, of three samples, produced results the mean average of which was significantly greater than 1.5 per cent.

35                  Although there was criticism of the November tests performed by Dr Lindquist, there is no apparent reason to doubt the outcome of the second series.  Dr McAlernon gave the following evidence in cross‑examination:

“Q.      Each of those experiments shows a water content of less than 1.5 per cent of course, doesn’t it?

 A.       Of course it does, yes.

 Q.       And would you accept those results?

 A.       I would.  Four repeats were carried out of essentially the same sample, and the four measurements that were carried out, if you calculate the relevant standard deviation as a percentage, it comes out at 1.4 per cent, which is acceptable as an RSD for a method that has been carried out, except you would expect an RSD of less than 1.5%.  I was very happy with the results that were determined in Sweden.”

36                  There was some controversy about the Brisbane tests; it was suggested that the results might have been affected by laboratory conditions, particularly humidity, or possibly other factors.  There is an additional difficulty, however, which is that although there was evidence, given on a highly confidential basis, of the provenance of the samples of the components of the Alphapharm product which were tested in Brisbane (and I think that evidence sufficiently demonstrated the provenance of those samples), I can find, and I was directed to, no evidence as to the provenance of the capsules which (and the contents of which) were subjected to the Brisbane tests.  Even if I accept that the capsules tested in Brisbane were indeed initially the same product as the admitted Alphapharm product tested in Sweden, I know nothing of the history of the capsules between manufacture and tests.  In those circumstances, the second series of tests in Sweden must be regarded as the more reliable.  That being so, the Alphapharm product falls within the terms of claim 10.  It may well be that that, whatever may be the future course of this proceeding, is unlikely to be a matter of any practical consequence.

(b)        Thickness of sub‑coat

37                  Claim 11 is for:

“A preparation according to any preceding claim, wherein said one or more subcoating layer(s) is not less than 2 microns thick.”

38                  In one of his experiments, Dr Lindquist bisected a pellet of the Alphapharm product, stained the omeprazole‑containing layer with hydrochloric acid and took a photomicrograph of the exposed surface.  Using a scale of measurement displayed on the photomicrograph, Dr Lindquist gave evidence that the middle layer (i.e. the sub‑coat) had a thickness of “about 15 to 20 microns”.  Dr Lindquist’s experiments, and his methods, were heavily criticised by Dr McAlernon.  Dr McAlernon disputed the correctness of Dr Lindquist’s measurement of the width of the sub‑coat.  Her evidence, however, was based upon a particular view of what the photomicrograph showed as the sub‑coat.  But she accepted  that she was not an expert in interpreting photomicrographs.  Professor Rees gave evidence in support of Dr Lindquist’s evidence on this point.  I saw the relevant portion of a video film of the experiments, and I have seen a copy of the photomicrograph and read and heard what the witnesses had to say about it.  There is a very large margin for error between two and fifteen microns.  I am satisfied that the sub‑coating layer of the Alphapharm product is not less than two microns thick.

Conclusion on infringement issues

39                  It follows that, assuming validity of the patent (contrary to my conclusion on obviousness), that which Alphapharm threatens to do would infringe claims 1, 4, 10, 11, 12, 13, 14, 15 and (making the additional assumption that claims 16 and 17 are not invalid because they are for a method of treating the human body) claims 16 and 17.

Conclusion

40                  The outcome of the proceeding, consistent with these reasons and my reasons on validity, is dealt with in the latter reasons.

Associate:

Dated:              12 October 1999